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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/30213530/toward-genome-editing-in-x-linked-rp-development-of-a-mouse-model-with-specific-treatment-relevant-features
#1
J Schlegel, J Hoffmann, D Röll, B Müller, S Günther, W Zhang, A Janise, C Vössing, B Fühler, J Neidhardt, H Khanna, B Lorenz, K Stieger
Genome editing represents a powerful tool to treat inherited disorders. Highly specific endonucleases induce a DNA double strand break near the mutant site, which is subsequently repaired by cellular DNA repair mechanisms that involve the presence of a wild type template DNA. In vivo applications of this strategy are still rare, in part due to the absence of appropriate animal models carrying human disease mutations and knowledge of the efficient targeting of endonucleases. Here we report the generation and characterization of a new mouse model for X-linked retinitis pigmentosa (XLRP) carrying a point mutation in the mutational hotspot exon ORF15 of the RPGR gene as well as a recognition site for the homing endonuclease I-SceI...
August 24, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30194922/the-role-of-gamma-delta-t-lymphocytes-in-breast-cancer-a-review
#2
REVIEW
Elizabeth S Morrow, Antonia Roseweir, Joanne Edwards
Gammadelta T (γδT) lymphocytes have provoked interest in oncology, particularly as regards their potential use in immunotherapy, because of their unique ability to recognise antigens without a requirement for major histocompatibility complex antigen presentation, and to quickly activate an anti-tumour response. However, work in some cancers has suggested that they also have pro-tumourigenic activity. Their role in breast cancer is unclear. This review outlines the evidence to date in in vitro studies, in vivo mouse models and in human studies regarding the role of γδT lymphocytes in breast cancer...
August 18, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30176239/changes-in-cdkn2a-2b-expression-associate-with-t-cell-phenotype-modulation-in-atherosclerosis-and-type-2-diabetes-mellitus
#3
Ángela VinuÉ, Sergio MartÍnez-HervÁs, Andrea Herrero-Cervera, Verónica SÁnchez-GarcÍa, Irene AndrÉs-Blasco, Laura Piqueras, MarÍa JesÚs Sanz, JosÉ TomÁs Real, Juan F Ascaso, Deborah Jane Burks, Herminia GonzÁlez-Navarro
Previous studies indicate a role of CDKN2A/2B/2BAS genes in atherosclerosis and type 2 diabetes mellitus (T2DM). Progression of these diseases is accompanied by T-cell imbalance and chronic inflammation. Our main objective was to investigate a potential association between CDKN2A/2B/2BAS gene expression and T cell phenotype in T2DM and coronary artery disease (CAD) in humans, and to explore the therapeutic potential of these genes to restore immune cell homeostasis and disease progression. Reduced mRNA levels of CDKN2A (p16Ink4a ), CDKN2B (p15Ink4b ), and CDKN2BAS were observed in human T2DM and T2DM-CAD subjects compared with controls...
August 15, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30176238/cell-and-size-specific-analysis-of-placental-extracellular-vesicles-in-maternal-plasma-and-pre-eclampsia
#4
REVIEW
Terry K Morgan
Despite decades of investigation, we cannot predict, prevent, or adequately treat the most common and deadly complications of pregnancy, including pre-eclampsia (pregnancy-induced hypertension). The current working hypothesis for the repeated failures of several multicenter studies that measured a wide variety of biomarkers is common pregnancy complications like pre-eclampsia are most likely heterogeneous syndromes with various etiologies; therefore, no combination of blood-based biomarkers will provide predictive power...
August 12, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30179587/precision-medicine-in-lupus-nephritis-can-biomarkers-get-us-there
#5
REVIEW
Dawn J Caster, Michael L Merchant, Jon B Klein, David W Powell
Patients with systemic lupus erythematosus frequently develop lupus nephritis (LN), a condition that can lead to end-stage kidney disease. Multiple serum and urine biomarkers for LN have been proposed in recent years, yet none have become incorporated into clinical use. The majority of studies have been single center with significant variability in cohorts, assays, and sample storage, leading to inconclusive results. It has become clear that no single biomarker is likely to be sufficient to diagnose LN, identify flares, and define the response to therapy and prognosis...
August 10, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30170004/dna-methylation-as-a-transcriptional-regulator-of-the-immune-system
#6
REVIEW
Luisa Morales-Nebreda, Fred S McLafferty, Benjamin D Singer
DNA methylation is a dynamic epigenetic modification with a prominent role in determining mammalian cell development, lineage identity, and transcriptional regulation. Primarily linked to gene silencing, novel technologies have expanded the ability to measure DNA methylation on a genome-wide scale and uncover context-dependent regulatory roles. The immune system is a prototypic model for studying how DNA methylation patterning modulates cell type- and stimulus-specific transcriptional programs. Preservation of host defense and organ homeostasis depends on fine-tuned epigenetic mechanisms controlling myeloid and lymphoid cell differentiation and function, which shape innate and adaptive immune responses...
August 9, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30165038/mitochondria-in-innate-immune-signaling
#7
REVIEW
Balaji Banoth, Suzanne L Cassel
Mitochondria are functionally versatile organelles. In addition to their conventional role of meeting the cell's energy requirements, mitochondria also actively regulate innate immune responses against infectious and sterile insults. Components of mitochondria, when released or exposed in response to dysfunction or damage, can be directly recognized by receptors of the innate immune system and trigger an immune response. In addition, despite initiation that may be independent from mitochondria, numerous innate immune responses are still subject to mitochondrial regulation as discrete steps of their signaling cascades occur on mitochondria or require mitochondrial components...
August 7, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30144425/mitochondrial-regulation-of-diabetic-vascular-disease-an-emerging-opportunity
#8
REVIEW
Michael E Widlansky, R Blake Hill
Diabetes-related vascular complication rates remain unacceptably high despite guideline-based medical therapies that are significantly more effective in individuals without diabetes. This critical gap represents an opportunity for researchers and clinicians to collaborate on targeting mechanisms and pathways that specifically contribute to vascular pathology in patients with diabetes mellitus. Dysfunctional mitochondria producing excessive mitochondrial reactive oxygen species (mtROS) play a proximal cell-signaling role in the development of vascular endothelial dysfunction in the setting of diabetes...
August 4, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30144424/serum-biomarkers-for-diagnosis-and-prediction-of-type-1-diabetes
#9
REVIEW
Lian Yi, Adam C Swensen, Wei-Jun Qian
Type 1 diabetes (T1D) culminates in the autoimmune destruction of the pancreatic β cells, leading to insufficient production of insulin and development of hyperglycemia. Serum biomarkers including a combination of glucose, glycated molecules, C-peptide, and autoantibodies have been well established for the diagnosis of T1D. However, these molecules often mark a late stage of the disease when ∼90% of the pancreatic insulin-producing β-cells have already been lost. With the prevalence of T1D increasing worldwide and because of the physical and psychological burden induced by this disease, there is a great need for prognostic biomarkers to predict T1D development or progression...
August 1, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30153426/mitochondrial-dynamics-in-skeletal-muscle-insulin-resistance-and-type-2-diabetes
#10
REVIEW
CiarÁn E Fealy, Anny Mulya, Christopher L Axelrod, John P Kirwan
The traditional view of mitochondria as isolated, spherical, energy producing organelles, is undergoing a revolutionary change. Emerging data show that mitochondria form a dynamic reticulum that is regulated by cycles of fission and fusion. The discovery of proteins that modulate these activities has led to important advances in understanding human disease. Here, we review the latest evidence that connects the emerging field of mitochondrial dynamics to skeletal muscle insulin resistance and propose some potential mechanisms that may explain the long debated link between mitochondria and the development of type 2 diabetes...
July 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30144423/targeting-mitochondria-in-cancer-current-concepts-and-immunotherapy-approaches
#11
REVIEW
Sergey Pustylnikov, Francesca Costabile, Silvia Beghi, Andrea Faccibene
An essential advantage during eukaryotic cell evolution was the acquisition of a network of mitochondria as a source of energy for cell metabolism and contrary to conventional wisdom, functional mitochondria are essential for the cancer cell. Multiple aspects of mitochondrial biology beyond bioenergetics support transformation including mitochondrial biogenesis, fission and fusion dynamics, cell death susceptibility, oxidative stress regulation, metabolism, and signaling. In cancer, the metabolism of cells is reprogrammed for energy generation from oxidative phosphorylation to aerobic glycolysis and impacts cancer mitochondrial function...
July 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30142308/molecular-discoveries-and-treatment-strategies-by-direct-reprogramming-in-cardiac-regeneration
#12
REVIEW
John H Werner, John H Rosenberg, John Y Um, Michael J Moulton, Devendra K Agrawal
Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive...
July 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30142307/triple-tyrosine-kinase-inhibition-attenuates-pulmonary-arterial-hypertension-and-neointimal-formation
#13
Anjira S Ambade, Birgit Jung, Dongwon Lee, Henri Doods, Dongmei Wu
The present study examined the effects of simultaneous inhibition of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptor signaling with BIBF1000, a novel triple tyrosine kinase inhibitor on preventing and reversing the progression of severe pulmonary arterial hypertension (PAH) in an experimental model in rats. Left pneumonectomized male Wistar rats were injected with monocrotaline to induce PAH. Treatment with BIBF1000 from day 1 to day 21 after monocrotaline injection attenuated PAH development, as evidenced by lower values for pulmonary artery pressure (mPAP), right ventricular pressure (RVSP), pulmonary arterial neointimal formation, and the ratio of right ventricular weight to left ventricular and septum weight [RV/(LV+S)] on day 21 compared to control rats...
July 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30118659/functional-characterization-of-alternatively-spliced-gsn-in-head-and-neck-squamous-cell-carcinoma
#14
Dylan Z Kelley, Emily L Flam, Theresa Guo, Ludmila V Danilova, Fernando T Zamuner, Craig Bohrson, Michael Considine, Eric J Windsor, Justin A Bishop, Chi Zhang, Wayne M Koch, David Sidransky, William H Westra, Christine H Chung, Joseph A Califano, Sarah Wheelan, Alexander V Favorov, Liliana Florea, Elana J Fertig, Daria A Gaykalova
We have recently performed the characterization of alternative splicing events (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of protein expression common for cancer cells. Such analysis demonstrated a high ASE prevalence among tumor samples, including tumor-specific alternative splicing in the GSN gene.In vitro studies confirmed that overall expression of either ASE-GSN or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation, whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular invasion...
July 26, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30118658/liquid-biopsies-for-management-of-pancreatic-cancer
#15
REVIEW
Mohamadmahdi Samandari, María Gil Juliá, Alistair Rice, Antonios Chronopoulos, Armando E Del Río Hernández
Pancreatic cancer is one of the main causes of cancer related deaths worldwide. It is asymptomatic at an early stage, and most diagnosis occurs when the disease is already at a late stage, by which time the tumor is nonresectable. In order to increase the overall survival of patients with pancreatic cancer, as well as to decrease the cancer burden, it is necessary to perform early diagnosis, prognosis stratifications and cancer monitoring using accurate, minimally invasive and cost-effective methods. Liquid biopsies seek to detect tumor-associated biomarkers in a variety of extractable body fluids and can help to monitor treatment response and disease progression, and even predict patient outcome...
July 26, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30102918/serum-noncholesterol-sterols-in-alzheimer-s-disease-the-helsinki-businessmen-study
#16
Chaiyasit Sittiwet, Piia Simonen, Markku J Nissinen, Helena Gylling, Timo E Strandberg
Cerebral cholesterol metabolism is perturbed in late-onset Alzheimer's disease (AD), but whether also the extracerebral cholesterol metabolism is perturbed is not known. Thus, we studied whole-body cholesterol synthesis and absorption with serum noncholesterol sterols in men without AD (n = 114) or with (n = 18) "pure" AD (no concomitant atherosclerotic cardiovascular disease) in a long-term cohort (the Helsinki Businessmen Study) of home-dwelling older men without lipid-lowering drugs and on their habitual home diet...
July 26, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30107156/macrophage-depletion-by-clodronate-attenuates-bone-morphogenetic-protein-7-induced-m2-macrophage-differentiation-and-improved-systolic-blood-velocity-in-atherosclerosis
#17
Heidi Shoulders, Kaley H Garner, Dinender K Singla
Bone morphogenetic protein-7 (BMP-7) affects the presence of macrophage subtypes in vitro and in vivo at an early stage of atherosclerosis (ATH); however, it remains unknown whether BMP-7 treatment affects the development and progression of ATH at a mid-stage of the disease. We therefore performed a Day 28 (D28) study to examine BMP-7's potential to affect monocyte differentiation. Atherosclerosis was developed in ApoE KO mice, and these animals were treated with intravenous injections of BMP-7 and/or liposomal clodronate (LC)...
July 25, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30080989/silencing-of-telomere-binding-protein-adrenocortical-dysplasia-acd-homolog-enhances-radiosensitivity-in-glioblastoma-cells
#18
Francesca Polito, Maria Cucinotta, Rosaria V Abbritti, Anna Brogna, Stefano Pergolizzi, Chiara Tomasello, Valeria Baresi, Flavio F Angileri, Rosamaria Di Giorgio, Alfredo Conti, Domenico La Torre, Antonino Germanò, M'hammed Aguennouz
Adrenocortical dysplasia (ACD) is a shelterin protein involved in the maintenance of telomere length and in cancer radioresistance. This study investigated the expression profile of ACD in human gliomas and its role in radioresistance of glioma cells. The expression of ACD was analyzed in 62 different grades of glioma tissues and correlated with prognosis. A radioresistant cell line was generated from U87MG cells. For mechanistic studies, ACD was inhibited by small interfering RNA-targeting ACD and the effect on cell radioresistance, telomerase activity, cyclinD1, caspase-3, hTERT, and BIRC1 was evaluated...
July 20, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30092207/liquid-biopsies-to-guide-therapeutic-decisions-in-rheumatoid-arthritis
#19
REVIEW
Roxana Coras, Rekha Narasimhan, Monica Guma
Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that has transitioned from a debilitating disease to a chronic, controllable disease. This has been possible due to the introduction of new treatment strategies like "treat-to-target," in which the clinician treats the patient aggressively enough to reach low disease activity or remission, and the introduction of new therapeutic agents, such as biological therapies, which can lead to the prevention of damage by early diagnosis and initiation of treatment...
July 19, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/30075099/circulating-tumor-cells-as-liquid-biopsies-to-understand-cancer-metastasis
#20
REVIEW
Dennis Woo, Min Yu
Circulating tumor cells (CTCs) are a subset of cancer cells that are shed from the primary or metastatic tumors into the bloodstream. CTCs are responsible for the establishment of blood-borne distant metastases but their rarity, estimated at one CTC per billion blood cells, presents the biggest technical barrier to their functional studies. Recent advances in CTC isolation technology have allowed for the reliable capture of CTCs from the whole blood of cancer patients. The ability to derive clinically relevant information from CTCs isolated through a blood draw allows for the monitoring of active disease, avoiding the invasiveness inherent to traditional biopsy techniques...
July 17, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
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